Michiteru Ohtani

Stereoselective high-performance liquid chromatographic determination of ketamine and its active metabolite, norketamine, in human plasma

A stereoselective high-performance liquid chromatographic method for the determination of the enantiomers of ketamine and its active metabolite, norketamine, in human plasma is described. The compounds were extracted from plasma by liquid-liquid extraction three times in a combination of cyclohexane with 2.5 M NaOH, 1 mM HCl and 1 M carbonate buffer. Stereoselective separation was achieved on a Chiralcel OD column with a mobile phase of n-hexane-2-propanol (98:2, v/v). The detection wavelength was 215 nm. The lower limits of the determination of the method were 5 ng/ml for ketamine and 10 ng/ml for norketamine. The intra- and inter-day coefficients of variation ranged from 2.9 to 9.8% and from 3.4 to 10.7% for all compounds, respectively. The method was sensitive and sufficiently reproducible for stereoselective monitoring of ketamine and norketamine in human plasma during pharmacokinetic studies after the administration of ketamine for analgesia.

Evaluation of Moisturizing Effect of Heparinoid Ointment (Hirudoid Soft Ointment) Diluted by White Petrolatum (Propeto)

Steroid ointments are frequently mixed with moisturizer. It was reported that steroid ointments mixed with moisturizer increase permeability. There are only few studies done on the permeability of the moisturizer. We researched moisturizing effect of heparinoid ointment (Hirudoid Soft ointment) diluted with white petrolatum (Propeto) on the dry skin models by measuring water content of stratum. Two to four fold dilution of Hirudoid to white petrolatum resulted in a significant decrease in the moisturizing effect of the active ingredient. There was no significant difference in moisturizing effect between four times diluted mixture and white petrolatum alone. This leads to the conclusion that steroid ointment mixture with moisturizer is frequently used, but we should take more caution regarding the decrease of moisturizing effect.

Improvement of the Convenience of White Petrolatum

White petrolatum is frequently used as an oleaginous base, but has a drawback of poor usability. In this trial, white petrolatum was prepared at a lower melting point to improve its usability. Characteristic pharmaceutical values such as melting point, yield, and consistency were compared between a conventional product and ophthalmic white petrolatum. Usability was compared by administering a survey questionnaire and evaluating the comparable moisturizing effect by conductivity in humans. The melting point and yield value of the improved product were significantly lower compared with other white petrolatum products. In the survey, the improved product was rated excellent in five criteria. On a scale of 1 to 5, the average values for the five criteria for the improved product were 4.7, while the conventional product and ophthalmic white petrolatum were rated 3.0 and 3.5, respectively. No difference in moisturizing effect was observed among all petrolatums after application, from day 1 to day 14. In conclusion, the improved white petrolatum demonstrated better usability, and the moisturizing effect was equivalent to conventional product, suggesting that the use of this improved product may lead to improved adherence.

Quantitative Analysis of the Effect of Mixing Conditions on Mixing Degree of Powder.

When phenytoin fine granules and diluted digoxin powder are mixed with diluents, an especially high uniformity of mixing is required in clinical practice. In the present study, a quantitative analysis was performed to evaluate of mixing properties of either phenytoin fine granules or diluted digoxin powder, using fine lactose and corn starch as the diluents (mixing ratio, 7: 3). Twenty grams each of phenytoin and the diluents was put into a mortar without sieving and then was mixed in a spiral manner with a pestle, while the mortar was fixed with the left hand on the dispensing table (method A) or the pastle was moved in the opposite direction (method B). At least 80 times of the mixing was required in method A to obtain a permissible limit of good mixing (less than 6.08% as the coefficients of variation (CV) of phenytoin), while only 60 times was required in the method B. In addition, the effect of sieving on the degree of mixing was also investigated. When 20 g each of digoxin and diluents was mixed by method B, the CV was more than 12% even after 80 times of mixing. However, when digoxin and the diluents were mixed after sieving (32 mesh, 500μm), the CV of digoxin decreased drastically and a permissible limit of good mixing was obtained at 60 times of mixing. These differences in the mixing efficiency with and without sieving could thus be explained by electron microscopic observations. On the other hand, in the case of phenytoin, sieving had scarcely any effect.Based on these results, in the case of phenytoin, at least 60 times of mixing with a pestle accompanied with the round movement of the mortar is required. On the other hand, in the case of digoxin which requires a high degree of mixing, the similar mixing after sieving is required.